Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model

Area of Science:

• Environmental Health Sciences
• Toxicology
• Biotechnology

Background:

• Exposure to estrogen receptor (ER) modulators poses health risks, necessitating identification of environmental disruptors.
• Current methods using cell monolayers lack accuracy in predicting in vivo endocrine disruptor potencies.
• There is a need for physiologically relevant models to assess tissue- or organ-level responses to ER modulators.

Purpose of the Study:

• To develop and evaluate a novel screening platform for quantitatively assessing ER modulators.
• To utilize 3D cultures on paper scaffolds for improved throughput and performance in toxicity screening.
• To assess the potential of this platform for environmental chemical risk assessment.

Main Methods:

• Developed a 96-well screening platform using chemically isolated 3D cultures supported by wax-patterned paper scaffolds.
• Quantified the potency of known ER modulators using a luciferase-based reporter assay.
• Measured the proliferation and invasion of ER-positive cell lines in the presence of estradiol.

Main Results:

• Successfully implemented a 3D culture system on paper scaffolds for high-throughput screening.
• Demonstrated the capability to measure ER modulator potency and cellular responses (proliferation, invasion).
• The current setup did not outperform monolayer cultures in predicting in vivo ER modulator potencies.

Conclusions:

• The paper-based scaffold platform demonstrates potential for screening environmental ER modulators.
• This technology can support increasingly complex, physiologically relevant tissue-like structures for risk assessment.
• Further development is needed to enhance predictive accuracy for in vivo responses.